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Toxicological information

Genetic toxicity: in vivo

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Administrative data

Endpoint:
in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus
Remarks:
Type of genotoxicity: chromosome aberration
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1987 to 1988
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study comparable to OECD Guideline.

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
1988

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
Deviations:
no
GLP compliance:
not specified
Type of assay:
micronucleus assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
as purchased by Aldrich Chemical Company, Milwaukee, WI, USA

Test animals

Species:
mouse
Strain:
Swiss Webster
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Simonsen Laboratories inc., Gilroy, CA, USA
- Age at study initiation: young adults
- Weight at study initiation: 20 to 30 g
- Assigned to test groups randomly: yes
- Fasting period before study: not reported
- Housing: 2-4/cage
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 5 days


ENVIRONMENTAL CONDITIONS
- Photoperiod (hrs dark / hrs light): 12/12


Administration / exposure

Route of administration:
oral: gavage
Vehicle:
- Vehicle(s)/solvent(s) used: 2% Castor oil, ethylene oxide reaction product (Emulphor EL-620), water
- Justification for choice of solvent/vehicle: solubility
- Concentration of test material in vehicle: depending on volume
- Amount of vehicle (if gavage or dermal): 1 ml/kg bw
Details on exposure:


PREPARATION OF DOSING SOLUTIONS: not reported
Duration of treatment / exposure:
twice at beginning of test and 24 hours apart
Frequency of treatment:
24 hours apart
Post exposure period:
48/72 h
Doses / concentrations
Remarks:
Doses / Concentrations:
3, 6, 12 mg/kg bw
Basis:
nominal conc.
No. of animals per sex per dose:
12 males and 12 females per dose (6 per sex to be evaluated after 48 and 6 to be evaluated 72 hours after treatment)
Control animals:
yes, concurrent vehicle
Positive control(s):
trimethylphosphate
- Justification for choice of positive control(s): not reported
- Route of administration: oral gavage
- Doses / concentrations:2 doses of 1250 mg/kg bw

Examinations

Tissues and cell types examined:
Femoral bone marrow
Details of tissue and slide preparation:
CRITERIA FOR DOSE SELECTION: toxicity of substance


TREATMENT AND SAMPLING TIMES ( in addition to information in specific fields):mice received 2 oral gavage administrations 24 hours apart; sampling time 48 and 72 hours after first treatment


DETAILS OF SLIDE PREPARATION:Bone marrow cell suspensions from both femurs were prepared in fetal bovine serum, snmeared on slides and stained in buffered Giemsa stain (pH 6.8). The prepared slides were coded aprior to analysis. At least 500 polychromatic errythrocytes (PCE)/animal were scored for the presence of micronuclei. The ratio of PCE to mature erythrocytes (RBC) was determined from the number of RBC encountered while scoring the first 200 PCE/animal

Evaluation criteria:
micronucleated PCE/500 PCE > 0.90 (p < 0.05)
Statistics:
Method of Mackey and MacGregor

Results and discussion

Test results
Sex:
male/female
Genotoxicity:
negative
Toxicity:
no effects
Vehicle controls validity:
valid
Negative controls validity:
valid
Positive controls validity:
valid
Additional information on results:
RESULTS OF RANGE-FINDING STUDY
- Dose range: not performed

RESULTS OF DEFINITIVE STUDY
- Induction of micronuclei (for Micronucleus assay): 0.04 to 0.18 %
- Ratio of PCE/NCE (for Micronucleus assay): 1.08 to 1.31

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): negative
Substance is not clastogenic in vivo to bone marrow under the conditions used.
Executive summary:

1,1,3 -Trichloroacetone was assessed for its capacity to induce micronuclei in the femur bone marrow of male and female Swiss-Webster mice. The substance was given twice by oral gavage to 4 groups of 12 males and 12 females at concentrations of 0, 3, 6 and 12 mg/kg bw. Another group received 1250 mg/kg bw trimethylphosphate as a control which worked as expected. No effect was seen on cytotoxicity the PCE/RBC ratio nor on the number of polymicronucleated PCE. The substance is not clastogenic in vivo to bone marrow cells of mice under the conditions used.